PROJECT SUMMARY Sexual minority (SM) individuals (e.g., those who identify as lesbian, gay, or bisexual) are substantially more likely than heterosexuals to experience internalizing psychopathology and associated comorbidity. Young and early adulthood (ages 18 to 34) represents the period during which significant sexual orientation disparities in internalizing psychopathology emerge. Yet, little is known about the biopsychosocial mechanisms underlying the sexual orientation disparity in mental disorders during this critical developmental stage. We have created a rare opportunity, currently unavailable in US-based studies, to address these knowledge gaps by capitalizing on three methodological advancements available in a large prospective, population-based dataset in Sweden: the Swedish National Public Health Survey (SNPHS). These advancements include the opportunity to: (1) follow back SM survey respondents sampled using probability designs; (2) match those SM respondents to a heterosexual comparison using registry data that contains objective records of sociodemographic and mental health characteristics shown to robustly predict internalizing psychopathology; and (3) link longitudinal biomarker data to mental health assessments. Capitalizing on these strengths, our research will address three aims. First, we will evaluate whether psychosocial mechanisms (e.g., negative self-schemas, attentional threat bias, social avoidance) explain the young adult SM disparity in internalizing psychopathology. We address this aim by following a new representative cohort of SM young adults ages 18-34 (N=673) and a matched heterosexual cohort (N=673) drawn from the SNPHS, which we will call the PLUS (Pathways to Longitudinally Understanding Stress) cohort. We will administer to this cohort an online battery of self-report and behavioral measures of internalizing psychopathology and proposed mechanisms for four years annually. Second, we will evaluate whether biological mechanisms explain the young adult SM disparity in internalizing psychopathology. To address this aim, we will collect biomarkers from the PLUS sample, which will be self-collected via the dried blood spot method. These biological measures will capture stress-sensitive inflammatory processes (C- reactive protein, IL-6, TNF?) implicated in internalizing psychopathology. Third, we will examine whether stigma-related reactions (e.g., identity concealment) and the biopsychosocial mechanisms identified in Aims 1 and 2 mediate the prospective association between stigma-related stress and internalizing psychopathology among SM young adults in the new PLUS cohort. Secondary analyses for all aims will examine the generalizability of our model to externalizing comorbidities and to intersectional populations of SM. Existing research, and our own pilot data, indicates that the results will generalize to understanding mechanisms underlying internalizing psychopathology among SM in the US and abroad. This theoretically informed, methodologically rigorous investigation permits the most comprehensive test of young adult SM mental health to date, allowing us to identify modifiable treatment targets to advance SM mental health.